Reevaluating the epinephrine myth: A comprehensive review.

ABSTRACT: The combination of local anesthetic drugs with epinephrine has conventionally been contraindicated in acral regions due to concerns of potential necrosis caused by compromised blood flow. However, this belief has been challenged since 2001, when studies demonstrated the safety and effectiveness of the combination. This review aims to analyze reported cases of acral area necrosis following the use of local anesthesia with epinephrine since 2001. A thorough search was conducted on PubMed and Google Scholar using specific keywords to identify articles reporting acral area necrosis caused using local anesthesia and epinephrine. Our search yielded eight publications describing a total of 13 cases of ischemic events in acral areas. These cases involved finger necrosis (five cases), scrotal skin necrosis (two cases), and eyelid necrosis (six cases), following the injection of a combination of epinephrine and lignocaine. The majority of affected patients were female who underwent surgical intervention and reconstruction. The use of epinephrine in local anesthesia offers significant advantages and is generally safe for acral areas. However, the risk of necrosis cannot be entirely eliminated, particularly in patients with compromised vascular function. Adhering to proper guidelines and selecting suitable patients can help mitigate the risk. Phentolamine serves as a potential rescue agent if vascular compromise occurs. Precautionary measures must be taken when using this combination in high-risk patients.

A Case Report and Pediatric Literature Review: Povidone as a Rare Cause of Anaphylaxis in Children.

Background: Povidone, a synthetic polymer commonly used in various products such as antiseptics, cosmetics, and medications, has been associated with allergic reactions, including anaphylaxis. Despite its widespread use, cases of povidone-induced anaphylaxis, especially in children, are under-recognized. This case report aims to highlight the importance of considering povidone allergy in pediatric patients presenting with anaphylaxis. Case Presentation: We describe a 3-year-old boy who experienced anaphylaxis following the application of povidone-iodine antiseptic solution to a leg wound. He presented with generalized urticaria, angioedema, dyspnea, and cough. Prompt diagnosis and management were initiated in the emergency department. He experienced the second anaphylaxis with povidone-containing eye drops prescribed during an ophthalmology visit. Conclusions: Povidone allergy should be considered in pediatric patients presenting with anaphylaxis, especially those with idiopathic reactions or multiple drug allergies. Clinicians should emphasize patient education on label reading and the provision of adrenaline autoinjectors to prevent life-threatening reactions associated with povidone exposure.

Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients- a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. METHODS: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. RESULTS: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically. CONCLUSION: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.

Perioperative anaphylactic shock caused by propofol.

Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose anaphylaxis and treat promptly with adrenaline and fluids. Allergy investigation should be performed subsequently. This is a case report of perioperative anaphylaxis to propofol. Propofol contains refined soya oil and egg lecithin, but no connection between allergy to soy, egg or peanut and allergy to propofol has been proven, and international guidelines recommend that propofol can be used in patients with these food allergies.

Limb Necrosis in the Setting of Vasopressor Use.

BACKGROUND: It remains poorly understood why only some hemodynamically unstable patients who receive aggressive treatment with vasopressor medications develop limb necrosis. OBJECTIVE: To determine the incidence of limb necrosis and the factors associated with it following high-dose vasopressor therapy. METHODS: A retrospective case-control medical records review was performed of patients aged 18 to 89 years who received vasopressor therapy between 2012 and 2021 in a single academic medical center. The study population was stratified by the development of limb necrosis following vasopressor use. Patients who experienced necrosis were compared with age- and sex-matched controls who did not experience necrosis. Demographic information, comorbidities, and medication details were recorded. RESULTS: The incidence of limb necrosis following vasopressor administration was 0.25%. Neither baseline demographics nor medical comorbidities differed significantly between groups. Necrosis was present in the same limb as the arterial catheter most often for femoral catheters. The vasopressor dose administered was significantly higher in the necrosis group than in the control group for ephedrine (P = .02) but not for the other agents. The duration of therapy was significantly longer in the necrosis group than in the control group for norepinephrine (P = .001), epinephrine (P = .04), and ephedrine (P = .01). The duration of vasopressin administration did not differ significantly between groups. CONCLUSION: The findings of this study suggest that medication-specific factors, rather than patient and disease characteristics, should guide clinical management of necrosis in the setting of vasopressor administration.

The effect of injection of 1:100 000 adrenaline solution in the pterygopalatine fossa on intra-operative bleeding during endoscopic sinonasal surgical procedures in chronic sinusitis: a blinded clinical trial.

OBJECTIVE: Rhinosinusitis is one of the most common reasons for a visit to otolaryngology clinics. Some patients are candidates for sinus surgery. Infiltration of 1:100 000 adrenaline in the pterygopalatine fossa was studied, with the aim of evaluating the effect on bleeding in the surgical field. METHODS: This double-blind clinical trial was conducted in 2021-2022 on 40 candidates for endoscopic sinus surgery. For each patient, one side of the pterygopalatine fossa was randomly selected to be infiltrated with a vasoconstrictor. Surgical field bleeding on each side was evaluated. RESULTS: Blood loss was 35.8 ± 20.9 ml in the study group and 38.4 ± 23.7 ml for the control group, with no statistically significant difference between groups (p = 0.49). In addition, there was no difference between the two groups in terms of the surgical field based on Boezaart scores. CONCLUSION: Although there are some recommendations on the usage of vasoconstrictors via the pterygopalatine foramen, debate remains.

[Extensive transfixing skin necrosis after breast biopsy under local anesthesia: About four cases]. / Nécrose cutanée étendue transfixiante après biopsie mammaire sous anesthésie locale : rapport de quatre cas.

INTRODUCTION: Local anesthetics with adrenaline are widely used in routine practice and have long proven their benefits and safety. The rare complications due to their use mainly concern immuno-allergic and vascular mechanisms. DESCRIPTION: In this article, we present four similar cases of early transfixing skin necrosis occurring after radioguided breast biopsy under local anesthesia using epinephrine local anesthetics in the context of a diagnostic approach to breast cancer. DISCUSSION: Although the literature is comforting about the use of local anesthetics, even on the extremities, severe skin complications continue to be reported sporadically. The analysis and understanding of these phenomena would allow, in the long run, to avoid them and to reduce their importance. CONCLUSION: The occurrence of skin necrosis after breast biopsy under radiographic control is rare and seems to be related to the local anesthetic procedure. Although similar cases have been reported in the literature, it does not seem possible today to conclude on the exact physiopathology of these complications. A better knowledge of the pathophysiology of these complications would help to avoid their occurrence in the future.

Icatibant averting mechanical ventilation in acute ischemic stroke patient with alteplase-induced orolingual angioedema.

BACKGROUND AND PURPOSE: Orolingual angioedema (OA) represents a rare but life-threatening complication among patients with acute ischemic stroke treated with intravenous thrombolysis with alteplase. Novel agents, including icatibant, are recommended in resistant patients with alteplase-induced OA who have failed to respond to first-line therapies including corticosteroids, antihistamines, and/or adrenaline. METHODS: We present a patient with alteplase-induced OA who showed substantial clinical improvement following the administration of icatibant. RESULTS: We describe a 71-year-old woman with known arterial hypertension under treatment with angiotensin-converting enzyme inhibitor, who presented with acute ischemic stroke in the territory of the right middle cerebral artery and received intravenous alteplase. During intravenous thrombolysis, the case was complicated with OA without any response to standard anaphylactic treatment including corticosteroids, dimetindene, and adrenaline. Thirty minutes after symptom onset, icatibant, a synthetic selective bradykinin B2-receptor antagonist, was administered subcutaneously. Substantial symptomatic resolution was observed only following the icatibant administration. CONCLUSIONS: This case highlights the effectiveness of icatibant in the acute management of alteplase-induced OA. In particular, icatibant administration, following first-line therapies including corticosteroids, antihistamines, and/or adrenaline, may avert tracheostomy and intubation in resistant and refractory cases with OA following intravenous thrombolysis for acute ischemic stroke.

Refractory cardiac arrest caused by type I Kounis syndrome treated with adrenaline and nicorandil: A case report.

RATIONALE: Kounis syndrome is a rare but life-threatening anaphylactic reaction that can lead to acute coronary syndrome and cardiac arrest, and requires prompt diagnosis. Adrenaline, which is used to treat anaphylaxis, may cause coronary vasoconstriction and worsen ischemia, whereas coronary vasodilators may dilate systemic vessels and exacerbate hypotension. Delayed diagnosis of Kounis syndrome and inadequate therapeutic intervention may thus lead to a poor outcome. PATIENT CONCERNS: A 59-year-old man was treated for sepsis due to a liver abscess. Following administration of daptomycin, the patient developed severe anaphylactic shock leading to refractory cardiac arrest. Because conventional cardiopulmonary resuscitation was ineffective, extracorporeal cardiopulmonary resuscitation was considered as an alternative approach. DIAGNOSES: On bedside monitoring during cardiopulmonary resuscitation, unexpected ST-segment elevation was found on lead II electrocardiogram. Accordingly, the patient was clinically diagnosed with Kounis syndrome. INTERVENTIONS: Nicorandil (6 mg/h), a coronary vasodilator with minimal blood pressure effects, was administered along with high doses of vasopressors, including adrenaline 0.2 µg/kg/min. OUTCOMES: After the initiation of nicorandil administration, the patient achieved return of spontaneous circulation and did not require extracorporeal cardiopulmonary resuscitation. Based on the elevated serum tryptase level, normal creatine kinase-MB range, and lack of stenosis on coronary angiography, the patient was definitively diagnosed with type I (coronary vasospasm) Kounis syndrome. He was subsequently transferred to the referring hospital without neurological sequelae. LESSONS: If anaphylaxis leads to refractory shock and cardiac arrest, ischemic changes on the electrocardiogram should be investigated to identify underlying Kounis syndrome. In addition to adrenaline, coronary dilators are the definitive treatment. Nicorandil may be a useful treatment option because of its minimal effect on blood pressure.

Bipolar haemostatic forceps versus standard therapy by haemoclip + / - epinephrine injection as initial endoscopic treatment in active non-variceal upper GI bleeding: study protocol for a prospective, randomized multicentre trial (BeBop-Trial).

BACKGROUND: Patients with active nonvariceal upper gastrointestinal bleeding (NVUGIB) usually require urgent endoscopic treatment. Standard therapy (ST) using haemoclip + / - epinephrine injection is not always successful. Bipolar haemostatic forceps (HemoStat/Pentax®) are an approved medical device for the treatment of gastrointestinal bleeding. However, their use as a primary endoscopic treatment for active NVUGIB has not yet been proven in a randomized prospective study. METHODS: This is a prospective, randomized, multicentre superiority trial (n ≥ 5). Patients with active NVUGIB will be randomized (1:1) to ST and to experimental therapy (ET) by application of bipolar haemostatic forceps. In the case of failed initial treatment within 15 min, crossover treatment will be attempted first. Rescue treatment (e.g. via over-the-scope-clip) will then be allowed after 30 min. All patients will also receive standard therapy with proton pump inhibitors. Forty-five patients per treatment arm are required to demonstrate an absolute difference of 25.4% with a power of 80% and a significance level of 0.05. DISCUSSION: The hypothesis of the study is that bipolar haemostatic forceps are superior to ST in terms of successful primary haemostasis and the absence of recurrent bleeding within 30 days (combined endpoint). The 1:1 randomization is also ethically justifiable for this study, as both procedures are approved for the intervention in question. To further increase the safety of the patients in the study, crossover treatment and rescue treatment are planned. The prospective design seems feasible in a reasonable time frame (recruitment period of 12 months), as nonvariceal upper gastrointestinal bleeding is common. Anticoagulants and/or antiplatelet drugs could be an important confounding factor in the statistical analysis that needs to be taken into account and calculated if necessary. In conclusion, this randomized, prospective, multicentre study could make an important contribution to answering the question of whether bipolar haemostatic forceps could be the first-line therapy in the endoscopic treatment of stage Forrest I a + b NVUGIB. TRIAL REGISTRATION: ClinicalTrials.gov NCT05353062. Registered on April 30 2022.

Chronic ß-adrenergic stress contributes to cardiomyopathy in rodents with collagen-induced arthritis.

Patients with rheumatoid arthritis (RA) have a much higher incidence of cardiac dysfunction, which contributes to the high mortality rate of RA despite anti-arthritic drug therapy. In this study, we investigated dynamic changes in cardiac function in classic animal models of RA and examined the potential effectors of RA-induced heart failure (HF). Collagen-induced arthritis (CIA) models were established in rats and mice. The cardiac function of CIA animals was dynamically monitored using echocardiography and haemodynamics. We showed that cardiac diastolic and systolic dysfunction occurred in CIA animals and persisted after joint inflammation and that serum proinflammatory cytokine (IL-1ß, TNF-α) levels were decreased. We did not find evidence of atherosclerosis (AS) in arthritic animals even though cardiomyopathy was significant. We observed that an impaired cardiac ß1AR-excitation contraction coupling signal was accompanied by sustained increases in blood epinephrine levels in CIA rats. Furthermore, serum epinephrine concentrations were positively correlated with the heart failure biomarker NT-proBNP in RA patients (r2 = +0.53, P < 0.0001). In CIA mice, treatment with the nonselective ßAR blocker carvedilol (2.5 mg·kg-1·d-1, for 4 weeks) or the specific GRK2 inhibitor paroxetine (2.5 mg·kg-1·d-1, for 4 weeks) effectively rescued heart function. We conclude that chronic and persistent ß-adrenergic stress in CIA animals is a significant contributor to cardiomyopathy, which may be a potential target for protecting RA patients against HF.

A Patient with Known Allergy to Local Anesthesia Presenting for a Dental Restoration.

Dentists should be equipped to treat an allergic reaction in a dental office, and in this scenario, the potential allergic reaction is noted after administration of a common local anesthetic lidocaine with epinephrine. The allergic reaction quickly escalates to a full-blown anaphylaxis, and the management of such an episode is detailed in this article.

A Comparative Analysis of Local Anesthetics: Injection Associated Pain and Duration of Anesthesia.

BACKGROUND: Local anesthesia administration is frequently the most painful step of dermatologic surgery. Identification of an anesthetic that minimizes infiltration pain and toxicity while maximizing duration of action would improve both patient satisfaction and procedural safety. This study compared eight local anesthetic solutions to identify the composition that minimizes infiltration pain, maximizes duration of effect, and minimizes amount of local anesthetic needed. METHODS: In a double-blinded study, thirty subjects were injected with eight local anesthetic solutions of varied concentrations of lidocaine, epinephrine, benzyl alcohol, and sodium bicarbonate. Infiltration pain was rated by subjects using a visual analog scale and duration of anesthesia was assessed by needle prick sensation every 15 minutes. RESULTS: Solutions 2, 7, and 8, were significantly less painful (P<0.001), though not statistically different from each other. Two of the three solutions were buffered 10:1 with sodium bicarbonate. Additionally, two of the three contained notably decreased concentrations of lidocaine, 0.091% and 0.083%, than traditionally used in practice. The use of benzyl alcohol did not result in a reduction of reported pain. The duration of action was equal among the solutions regardless of anesthetic concentration. CONCLUSIONS: A solution of 0.091% lidocaine with epinephrine 1:1,100,000 and 0.82% benzyl alcohol reduces medication dose while ensuring maximum patient comfort and, theoretically, increases shelf life. While considered off-label, clinically effective dermal anesthesia may be obtained at a lower concentration of lidocaine and epinephrine than is commonly used, aiding conservative use of local anesthetic, particularly during times of national shortage. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.5183 Citation: Moses A, Klager S, Weinstein A, et al. A comparative analysis of local anesthetics: Injection associated pain and duration of anesthesia. J Drugs Dermatol. 2023;22(4):364-368. doi:10.36849/JDD.5183.

Contrast-induced anaphylaxis: does it occur in the medical environment and is it being responded to appropriately?

PURPOSE: To analyze the appropriateness of primary response for anaphylaxis due to iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCA). MATERIALS AND METHODS: This retrospective study included all patients in whom intravenous contrast agents (five types of ICMs and four types of GBCAs) were administered at our hospital between April 2016 and September 2021. For the patients who developed anaphylaxis, we obtained data on the time records of contrast injection, anaphylaxis onset, and intramuscular adrenaline (epinephrine) administration. RESULTS: Of the 76,555 ICM and 30,731 GBCA administrations, anaphylaxis occurred in 49 cases (0.05%), and in 48 cases (98.0%) the onset was within 30 min after administration with widely distributed times (median, 7.5 min; interquartile range, 4.5-10.8 min; max, 26 min). Intramuscular adrenaline administration was performed in 43 cases (87.8%), and this was done within five minutes after the onset in 37 cases (75.5%). Only in 24 cases (49.0%), there were time records of both the onset and adrenaline administration (if performed). CONCLUSION: Anaphylaxis occurred within 30 min after contrast injection in the majority of the cases, but times were widely distributed. Only in 75.5% of cases, appropriate primary treatment was performed, and the importance of keeping exact time records in patients' charts should be re-emphasized.

Efficacy and safety of intracoronary epinephrine for the management of the no-reflow phenomenon following percutaneous coronary interventions: a systematic-review study.

BACKGROUND: Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon. OBJECTIVES: To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents. DESIGN: Systematic review. DATA SOURCES AND METHODS: PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review. RESULTS: Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% versus 52.7%, respectively; p value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% versus 26.7%, respectively; p value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine. CONCLUSION: Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.